1. Field of the Invention
Therapeutic methods for control of low blood sugar levels in warm blooded animals, including humans.
2. Information Disclosure Statement
Glucose in the blood is a primary energy nutrient for the body. Its level in the blood is carefully controlled so that it neither goes too high nor too low. Maintaining a constant blood level of glucose is so important that the body has, within the limits of current understanding of physiology, surprisingly sophisticated hormonal systems to prevent both hyperglycemia (blood glucose too high) and hypoglycemia (blood glucose too low).
The body has diseases that are characterized by blood glucose levels that are either too high (i.e., Diabetes Mellitus types I and II) or too low (i.e., hypoglycemia). This disclosure describes improved therapeutic means to correct abnormally depressed blood glucose levels.
This invention recognizes the etiologies of these diseases of glucose metabolism. In order to understand the use of these new therapeutic inventions, it is necessary to describe the normal physiological control mechanisms of the body. Once they are understood, the etiologies of the disease states of hypoglycemia can be recognized. Finally, with all of this knowledge in place, the new therapies can be described.
Glucose is the main energy substance of the body and the blood is the means for transporting it to the various parts of the body. The blood glucose may be elevated by increasing its supply or blocking its removal. Conversely, blood glucose may be decreased by blocking its supply or enhancing its rate of removal from the blood.
There are two sources of blood glucose. Food contains glucose, usually ingested in the form of starch or dissaccharides and is converted to glucose by enzymes. The liver can also synthesize glucose from other food nutrients such as simple sugars or amino acids which are derived from protein digestion. Therefore, the blood level of glucose is a summation of the functions of its rate of entry into the blood and its rate of removal. The prior means of control of the blood level is summarized as follows:
______________________________________ Prior Knowledge Limits in Regulation of Blood Glucose Levels Factors that Lower Factors that Elevate Glucose Blood Glucose ______________________________________ 1. Ingested Food 1. Fasting and Exercise (i.e., starch, sugar) 2. Hepatic Glucose Production 2. Hormone Stimulated a. Glucose release from Glucose removal glycogen stimulated by from blood. glucagon, nor-epinephrine a. Insulin stimulates muscle or epinephrine. and fat cells to take up glucose. b. Glucose synthesized by 3. Hormone medicated glucagon stimulation inhibition of hepatic from protein. glucose production. a. Insulin alone inhibits the glucagon stimulated pro- duction of glucose by the liver - both synthesis and release. ______________________________________
Insulin is a well-known polypeptide hormone that was discovered in 1922. Insulin is released from the beta cells of the pancreas in response to elevated blood glucose. Insulin has the known actions of (1) inhibiting the denovo synthesis and release of glucose from the liver and (2) stimulating the uptake of glucose by muscle and fat tissues. Therefore, insulin has the net effect of lowering blood glucose. This invention has its genesis in the recognition that although it is commonly known that the liver stores ingested glucose as glycogen, the hormonal control mechanism for this glucose storage of glycogen has been unknown.
It has been hypothesized that insulin must stimulate the hepatic deposition of glycogen. However, the addition of insulin alone to liver tissue bathed in glucose solutions does not result in glycogen storage as is seen when insulin is added to muscle tissue bathed in a glucose solution. Prior to the discovery upon which the present invention is based, experts in the actions of insulin, based upon many scientific studies, attribute it to be simply an inhibitor of hepatic glucose production.